Serine ADP-ribosylation in genome stability and human disease

Proteins perform the majority of biological functions within a cell. They can act as enzymes, transporters, scaffolds to attract other proteins, and they can also replicate DNA. DNA contains the codes for proteins and their disruption and/or deregulation is associated with a range of human diseases, including cancer, neurodegenerative and autoimmune disorders. The control of protein functions occurs at many levels, including before a protein has been made, known as transcriptional regulation, and after, known as post-translational modification (PTM).

We will primarily focus on the PTM called ADP-ribosylation that is synthesised by enzymes called poly (ADP-ribose) polymerases (PARPs). PARPs are thought to control processes that are important for genome stability such as DNA repair and cell division. We aim to understand the exact mechanisms that enable timely synthesis and removal of ADP-ribosylation signals in cells.

Our research will help find ways that these processes can be exploited in the treatment of human disease.